Over-expression of Runx1 transcription factor impairs the development of thymocytes from the double-negative to double-positive stages.

Immunology
Won Fen WongMasanobu Satake

Abstract

Runx1 transcription factor is highly expressed at a CD4/CD8-double-negative (DN) stage of thymocyte development but is down-regulated when cells proceed to the double-positive (DP) stage. In the present study, we examined whether the down-regulation of Runx1 is necessary for thymocyte differentiation from the DN to DP stage. When Runx1 was artificially over-expressed in thymocytes by Lck-driven Cre, the DN3 population was unaffected, as exemplified by proper pre-T-cell receptor expression, whereas the DN4 population was perturbed as shown by the decrease in the CD27(hi) sub-fraction. In parallel, the growth rate of DN4 cells was reduced by half, as measured by bromodeoxyuridine incorporation. These events impaired the transition of DN4 cells to the DP stage, resulting in the drastic reduction of the number of DP thymocytes. The Runx1 gene has two promoters, a proximal and a distal promoter; and, in thymocytes, endogenous Runx1 was mainly transcribed from the distal promoter. Interestingly, only distal, but not proximal, Runx1 over-expression exhibited an inhibitory effect on thymocyte differentiation, suggesting that the distal Runx1 protein may fulfil a unique function. Our collective results indicate that production of the di...Continue Reading

References

Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·K ArakiP Vassalli
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·M C GhoziY Groner
May 14, 1999·Current Opinion in Immunology·H von BoehmerO Azogui
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·K HayashiM Satake
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·François VaillantEwan R Cameron
Jun 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Eilon WoolfYoram Groner
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Makoto SenooSonoko Habu
Aug 30, 2003·Immunology Letters·Takehito SatoSonoko Habu
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Janice C TelferEllen V Rothenberg
May 25, 2004·Oncogene·Ditsa Levanon, Yoram Groner
Aug 18, 2004·The Journal of Experimental Medicine·Thomas M SchmittJuan Carlos Zúñiga-Pflücker
Jun 7, 2005·Developmental Biology·Zhousheng XiaoLeigh Darryl Quarles
Jun 27, 2006·Developmental Biology·Naoko KanataniToshihisa Komori
Apr 19, 2007·Nature Immunology·Ellen V Rothenberg
Jun 9, 2007·The FEBS Journal·David D ChungDavid Wotton
Jul 25, 2007·The Journal of Experimental Medicine·Takeshi EgawaDan R Littman
Dec 22, 2007·Nature Reviews. Immunology·Ellen V RothenbergMary A Yui
Apr 11, 2008·Nature·J Jeremiah Bell, Avinash Bhandoola
Apr 11, 2008·Nature·Haruka WadaHiroshi Kawamoto
Mar 10, 2009·Blood Cells, Molecules & Diseases·Karen BlythEwan R Cameron

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Citations

Dec 21, 2012·Nucleic Acids Research·Gareth BradyPaul J Farrell
Mar 24, 2011·Leukemia & Lymphoma·Stefan NagelRoderick A F Macleod
Jul 5, 2013·Experimental Hematology·Christopher R DowdyGary S Stein
Dec 7, 2013·European Journal of Immunology·Won Fen WongKazuyoshi Kohu
Apr 22, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Divya K Shah, Juan Carlos Zúñiga-Pflücker

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